Koichi Tomoda

Correlation between accelerated presbycusis and decreased immune functions

The aim of the current study is to analyze the relationship between presbycusis and the immune system, which is affected by pathogenic environments, and to devise a strategy for the prevention of presbycusis using the SAMP1 mouse, an animal model for accelerated senescence that shows both immunological dysfunction and hearing loss caused by the impairment of spiral ganglion cells in the cochlea. When these mice were bred in different pathogenic environments, we found that the development of age-related diseases such as presbycusis was delayed in the mice bred under clean conditions. Prednisolone administration showed no significant prevention of the development of presbycusis in the mice, suggesting that autoimmune mechanisms are not involved in the acceleration of presbycusis. It is conceivable that pathogen-induced infections impose a severe stress on the host, impairing the hosts immune functions. A reduction in the number of pathogens may therefore prevent the acceleration of the aging process. These findings suggest that not only the gene backgrounds but also immune functions affect the development of presbycusis in SAMP1 mice. Further studies into the relationship between systemic immune functions and the neuro-generation system may provide additional information about the treatment for age-related diseases.

Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells

Induction of immune-mediated hearing loss in SCID mice by injection of MRL/lpr mouse spleen cells The MRL/lpr mouse, which has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, shows an accumulation of abnormal immunocompetent cells and SLE-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of injecting MRL/lpr spleen cells on the development of SHL in severe combined immunodeficient (SCID) mice, which originally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology were, indeed, transferred to the SCID mice by the injection of spleen cells from the MRL/lpr mice. These findings suggest that cell-mediated immunity is involved in the development of SHL and cochlear pathology.

Secondary Shunt Procedure for Alaryngeal Patients in an Outpatient Clinic

The shunt procedure used for laryngectomized patients undergoing secondary tracheo-esophageal (T-E) puncture is inconvenient and causes stress to the patient. In order to overcome these problems we developed a novel surgical T-E shunt technique using the Groningen voice prosthesis that does not require esophagoscopy or general anesthesia and can be performed in an outpatient clinic. In this procedure, a shunt is created using a pair of nasal forceps with the patient seated. An endoscope with biopsy forceps is used to insert the Groningen voice prosthesis. The procedure is usually completed within 20 min after inducing local anesthesia. Neither the technique itself nor the time taken to complete the procedure differed for T-E and tracheo-neoesophageal (reconstructed with flap) shunting. We believe that this procedure is suitable for patients who are afraid of esophagoscopy and/or are not considered suitable candidates for esophagoscopy and repeated general anesthesia. The procedure is also beneficial for both patients and surgeons with regard to its duration and the cost-effectiveness of treatment.

Evaluation of pharyngolaryngeal region with 3-D computed tomography

Abstract We present a new method of 3-D CT reconstruction with space extraction (volume rendering) technique in this study. The objective of this study is to demonstrate pharyngeal space with 3-D CT images and evaluate the volume change of upper airway in normal individuals and patients with snoring and sleep apnea. Axial CT scanning was taken before 3-D images of upper airway cavity being reconstructed. Then the volume of airway was measured, in each aspect of inspiration, expiration, sleeping, snoring and apnea. Repeat of closing and widening of airway was clearly demonstrated in OSAS (sleep apnea syndrome) patients during their sleep. It was also found that the volume changes of airway corresponded with shape changes. This new method is expected to be helpful in locating obstructive site and estimating surgical outcome of OSAS.

Bone marrow cells as an origin of immune-mediated hearing loss

The MRL/lpr mouse, which is homozygous for the recessive lpr genes and has a mutation in the Fas gene encoding a cell-surface receptor for apoptosis, exhibits severe lymphadenopathy and develops systemic lupus erythematosus (SLE)-like disease. It has recently been reported that this mouse also manifests sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We examined the effects of reconstituting severe combined immunodeficient (SCID) mice with MRL/lpr bone marrow on the development of SHL. These mice normally develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear pathology did, indeed, occur following transfer of MRL/lpr bone marrow into SCID mice. These findings suggest that the development of SHL and cochlear pathology observed in MRL/lpr mice and in SCID mice receiving MRL/lpr bone marrow are the result of bone marrow defects rather than the result of a problem intrinsic to the cochlea.

Peaceful and Contented Mind

Since 2002, we have started to accept the doctors from Indonesia or Bangladesh as a program for clinical training by the courtesy of Prof. Jun-Ichi Suzuki. Today, I wish to write my impression of them through the program. The doctors visited us were listed below.

Modifying effects of dietary flavonoid morin on 4-nitroquinoline 1-oxide-induced oral tumorigenesis

lized, immunoprecipitated, and sequentially immunoblotted using antibodies to mucin and transmembrane subunits. Results: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 24 of 29 primary UADT SCC, and in 6 of 6 metastatic cervical lymph nodes. A trend toward decreased staining of MUC4 in poorly differentiated tumors is suggested. Immunoblots show MUC4 in normal and tumor tissue in 3 of 4 SCCs analyzed, although electrophoretic migration patterns are similar between normal and tumor. Immunocytochemical staining of MUC4 in 11 major and minor salivary gland neoplasms reveals variable staining of normal and neoplastic tissue. MUC4 is consistently demonstrated in immunoblots of normal parotid tissue. Immunoblot with a carbohydrate-dependent antibody suggests carbohydrate differences in the MUC4 mucin subunit expressed in normal and neoplastic tissue from one parotid tumor. Conclusion: MUC4 is identified in SCCs of the UADT and neoplastic salivary tissue. Differential expression between normal and tumor MUC4 is demonstrated in some cases. Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors.